Introduction Directory UMM :Data Elmu:jurnal:A:Atherosclerosis:Vol152.Issue1.Sep2000:

Atherosclerosis 152 2000 239 – 248 The contribution of candidate genes to the response of plasma lipids and lipoproteins to dietary challenge Yechiel Friedlander a , Eran Leitersdorf b, , Roni Vecsler a , Harald Funke c , Jeremy Kark a a The Department of Social Medicine, The Hebrew Uni6ersity-Hadassah School of Public Health, Jerusalem, Israel b The Department of Medicine, Hadassah Uni6ersity Hospital, PO Box 12221 , 91120 Jerusalem, Israel c Institute of Clinical Chemistry and Laboratory Medicine, Uni6ersity of Munster, Munster, Germany Received 7 June 1999; received in revised form 19 October 1999; accepted 2 November 1999 Abstract The possible role of four candidate genes in lipid and lipoprotein response to diet was examined in 214 members of two large kibbutz settlements in Israel. Four site polymorphisms signal peptide insertiondeletion, XbaI, EcoRI and MspI of the apo B gene, the common apo E genotypes, three common mutations T-93G, S447stop and N291S of the LPL gene and the CETP I405V RFLP were determined. The average reduction induced by diet in participants with the absence of the EcoRI restriction site L4154 of the apo B gene compared with those found to be homozygotes for the restriction site GG4154 were: 16.2 and 8.0 mgdl for total cholesterol TC P = 0.01; and 15.6 and 6.2 mgdl for LDL-C P = 0.007, respectively. TC and LDL-C baseline levels were significantly different among the apo-E genotypes, yet there were no significant effects on lipid and lipoprotein dietary response. Triglyceride baseline values were significantly lower P = 0.007 among subjects with the LPL S447stop mutation and HDL-C was significantly lower P = 0.008 among subjects found to be heterozygous for the LPL N291S mutation. A heterogeneous response for triglyceride was observed for individuals with the S291 allele as compared to those individuals who were found to be homozygous for the N291 allele. No differences in dietary responsiveness were observed among the apo E and CETP genotypes. In conclusion, our results suggest that sequence variations in the coding region of the apo B gene linked to the EcoRI polymorphism are associated with total cholesterol and LDL-C responsiveness to dietary manipulation. In our study population, LPL mutations had a significant effect on TG and HDL-C baseline levels and on their response to diet. © 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords : Lipids; Lipoproteins; Genetics; Diet www.elsevier.comlocateatherosclerosis

1. Introduction

Levels of plasma lipids and lipoproteins can be al- tered by diet and the magnitude of dietary effects varies between individuals [1 – 4]. These differences could re- sult from different dietary adherence or may be due to true inter-individual variation in the response [1,5]. Other factors that may influence the response include sex [6], age [7], BMI [8] and the basal level of plasma lipids [9]. It is well established that genetic variation con- tributes to the basal plasma levels of lipids and lipo- proteins. Various studies have shown an association between lipid and lipoprotein levels and the apolipo- protein B apo-B RFLPs [10 – 14], however this has not been consistent [15,16]. In addition, studies have indi- cated that the apo E polymorphism influences plasma lipid levels [17]. Recent studies have shown that varia- tion at the lipoprotein lipase LPL and at the choles- terol ester transfer protein CETP loci also contribute to between-individual variation in plasma lipid and lipoprotein levels within the normal population [18 – 22]. It has been proposed that genetic variation may also contribute to the variability of these levels over time and in response to environmental exposure [23 – 26]. Corresponding author. Tel.: + 972-2-6778029; fax: + 972-2- 6411136. E-mail address : eranlhadassah.org.il E. Leitersdorf. 0021-915000 - see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 0 2 1 - 9 1 5 0 9 9 0 0 4 7 4 - 8 Recent studies provided evidence that genetic variabil- ity at apolipoprotein gene loci may contribute to the variation in lipid and lipoprotein response to dietary manipulations [27 – 36]. The present study examined the association between genotypes at the apo B, apo E, LPL and CETP loci with the response of plasma lipids and lipoproteins to dietary manipulation. This was carried out in 214 indi- viduals who participated in dietary experiments in which fatty acid composition and cholesterol intake were modified while total energy intake remained constant.

2. Material and methods